Amelioration of chronic cyclosporine A-induced nephrotoxicity by telmisartan in rats

Nephrotoxicity is a major problem of Cyclosporine A (CsA) treatment, despite its beneficial role in organ transplantation and in a variety of immunologic disorders. This study was undertaken to investigate the potential renoprotective role of telmisartan in amelioration of chronic CsA induced nephrotoxicity. The rats were randomized into 4 equal groups. Group 1 received normal saline (control), group 2 received Cremophor EL and ethanol (CsA vehicle), group 3 received CsA 25 mg/kg/day s.c and group 4 received telmisartan 3 mg/kg/day orally in addition to CsA. The rats were pair fed with a standard chow diet throughout the experiment period (8 weeks). CsA nephrotoxicity was assessed in terms of increased S.Cr (from 0.52± 0.16 to 1.29 ± 0.20 mg/ml), blood urea (from 24.69 ± 1.89 to 75.88± 2.33 mg/ml) and serum K (from 3.43 ± 0.18 to 5.23 ± 0.43 meq/l). CsA also caused significant increase (p<0.01) in MDA (from 0.74 ± 0.13 to 2.96 ± 0.43 nmol/mg protein) and significant decrease (p<0.01) in GSH and catalase in renal tissue. Telmisartan failed to restore the altered renal functions. On the other hand, it causes a significant improvement in the histological changes including the tubulointerstitial fibrosis and arteriolopathy (p<0.01). It also caused significant reduction (p<0.01) in CsA-induced oxidative stress. These findings suggested that telmisartan has a promising renoprotective effect against chronic CsA induced nephrotoxicity.   Key words: Cyclosporine A, nephrotoxicity, oxidative stress, telmisartan.